The influence of estrogen receptor α signaling independent of the estrogen response element on avoidance behavior, social interactions, and palatable ingestive behavior in female mice

Nov 8, 2021Hormones and behavior

Estrogen receptor alpha signals without DNA binding may affect avoidance, social behavior, and sweet eating in female mice

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Abstract

ERα signaling may influence social behaviors and food intake in females, with differences observed between knockout and knock-in models.

ERα does not appear to control anxiety-like behaviors but affects locomotor activity.
E2 may enhance social preference and recognition memory in females with a specific ERα variant but not in those lacking ERα.
KIKO females treated with oil showed increased consumption of high-fat food, while KO females exhibited delayed food intake.
The findings suggest that some social behaviors could be regulated by signaling pathways independent of the estrogen response element.

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Women are vulnerable to developing mental disorders that are associated with circulating estrogens. Estrogens, especially 17β-estradiol (E2), have a wide array of effects on the brain, affecting many behavioral endpoints associated with mental illness. By using a total estrogen receptor (ER) α knockout (KO), an ERα knock in/knock out (KIKO) that lacks a functional DNA-binding domain, and wild type (WT) controls treated with either oil or E2, we evaluated ERα signaling, dependent and independent of the estrogen response element (ERE), on avoidance behavior, social interactions and memory, and palatable ingestive behavior using the open field test, the elevated plus maze, the light dark box, the 3-chamber test, and palatable feeding. We found that ERα does not mediate control of anxiety-like behaviors but rather yielded differences in locomotor activity. In evaluating social preference and social recognition memory, we observed that E2 may modulate these measures in KIKO females but not KO females, suggesting that ERE-independent signaling is likely involved in sociability. Lastly, observations of palatable (high-fat) food intake suggested an increase in palatable eating behavior in oil-treated KIKO females. Oil-treated KO females had a longer latency to food intake, indicative of an anhedonic phenotype compared to oil-treated WT and KIKO females. We have observed that social-related behaviors are potentially influenced by ERE-independent ERα signaling and hedonic food intake requires signaling of ERα.

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The influence of estrogen receptor α signaling independent of the estrogen response element on avoidance behavior, social interactions, and palatable ingestive behavior in female mice

Abstract

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